Editing Telomere (section)

== Discovery ==
The existence of a special structure at the ends of chromosomes was independently proposed in 1938 by [[Hermann Joseph Muller]], studying the fruit fly ''[[Drosophila melanogaster]]'', and in 1939 by [[Barbara McClintock]], working with maize.<ref>{{Cite journal |last1=Varela |first1=E. |last2=Blasco |first2=M. A. |date=March 2010 |title=2009 Nobel Prize in Physiology or Medicine: telomeres and telomerase |url=https://www.nature.com/articles/onc201015 |journal=Oncogene |language=en |volume=29 |issue=11 |pages=1561–1565 |doi=10.1038/onc.2010.15 |pmid=20237481 |s2cid=11726588 |issn=1476-5594}}</ref> Muller observed that the ends of irradiated fruit fly chromosomes did not present alterations such as deletions or inversions. He hypothesized the presence of a protective cap, which he coined "telomeres", from the Greek ''telos'' (end) and ''meros'' (part).<ref>{{Cite book |last=Muller |first=H.J. |title=The Remaking of Chromosomes |publisher=Woods Hole |year=1938 |pages=181–198}}</ref>

In the early 1970s, Soviet theorist [[Alexey Olovnikov]] first recognized that chromosomes could not completely replicate their ends; this is known as the "end replication problem". Building on this, and accommodating [[Leonard Hayflick]]'s idea of limited [[somatic cell]] division, Olovnikov suggested that DNA sequences are lost every time a cell replicates until the loss reaches a critical level, at which point cell division ends.<ref>{{Cite journal |last=Olovnikov |first=A. M. |date=1971 |title=[Principle of marginotomy in template synthesis of polynucleotides] |url=https://pubmed.ncbi.nlm.nih.gov/5158754/ |journal=Doklady Akademii Nauk SSSR |volume=201 |issue=6 |pages=1496–1499 |issn=0002-3264 |pmid=5158754}}</ref><ref>{{Cite journal |last=Olovnikov |first=A. M. |date=1973-09-14 |title=A theory of marginotomy: The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon |url=https://dx.doi.org/10.1016/0022-5193%2873%2990198-7 |journal=Journal of Theoretical Biology |language=en |volume=41 |issue=1 |pages=181–190 |doi=10.1016/0022-5193(73)90198-7 |pmid=4754905 |bibcode=1973JThBi..41..181O |issn=0022-5193}}</ref><ref>{{Cite journal |last=Olovnikov |first=A. M. |date=1996 |title=Telomeres, telomerase, and aging: origin of the theory |url=https://pubmed.ncbi.nlm.nih.gov/9415101/ |journal=Experimental Gerontology |volume=31 |issue=4 |pages=443–448 |doi=10.1016/0531-5565(96)00005-8 |issn=0531-5565 |pmid=9415101|s2cid=26381790 }}</ref> According to his theory of marginotomy, DNA sequences at the ends of telomeres are represented by tandem repeats, which create a buffer that determines the number of divisions that a certain cell clone can undergo. Furthermore, it was predicted that a specialized DNA polymerase (originally called a tandem-DNA-polymerase) could extend telomeres in immortal tissues such as germ line, cancer cells and stem cells. It also followed from this hypothesis that organisms with circular genome, such as bacteria, do not have the end replication problem and therefore do not age.

Olovnikov suggested that in germline cells, cells of vegetatively propagated organisms, and immortal cell populations such as most cancer cell lines, an enzyme might be activated to prevent the shortening of DNA termini with each cell division.<ref>{{Cite journal |last=Olovnikov |first=I. A. |date=2023 |title=[«He always talked about something else…» Alexey Matveyevich Olovnikov and his unusual science.] |url=https://pubmed.ncbi.nlm.nih.gov/37356090/ |journal=Advances in Gerontology = Uspekhi Gerontologii |volume=36 |issue=2 |pages=162–167 |doi=10.34922/AE.2023.36.2.001 |issn=1561-9125 |pmid=37356090}}</ref><ref>{{Cite web |title=Library Index |url=https://olovnikov.com/library/libraryindex.php |access-date=2024-10-13 |website=olovnikov.com}}</ref>

In 1975–1977, [[Elizabeth Blackburn]], working as a postdoctoral fellow at [[Yale University]] with [[Joseph G. Gall]], discovered the unusual nature of telomeres, with their simple repeated DNA sequences composing chromosome ends.<ref name=":0">{{cite journal | vauthors = Blackburn EH, Gall JG | title = A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena | journal = Journal of Molecular Biology | volume = 120 | issue = 1 | pages = 33–53 | date = March 1978 | pmid = 642006 | doi = 10.1016/0022-2836(78)90294-2 }}</ref> Blackburn, [[Carol Greider]], and [[Jack Szostak]] were awarded the [[List of Nobel laureates in Physiology or Medicine#2001–current|2009]] [[Nobel Prize in Physiology or Medicine]] for the discovery of how chromosomes are protected by telomeres and the [[enzyme]] [[telomerase]].<ref>{{cite web|url=http://nobelprize.org/nobel_prizes/medicine/laureates/2009/press.html |title=Elizabeth H. Blackburn, Carol W. Greider, Jack W. Szostak: The Nobel Prize in Physiology or Medicine 2009 |publisher=Nobel Foundation |date=2009-10-05 |access-date=2012-06-12}}</ref>